Reciprocal activation of cancer-associated fibroblasts and oral squamous carcinoma cells through CXCL1.
Oral Oncol
; 88: 115-123, 2019 01.
Article
in En
| MEDLINE
| ID: mdl-30616781
ABSTRACT
OBJECTIVES:
Crosstalk between cancer cells and carcinoma-associated fibroblasts (CAFs) is known to be involved in various aspects of tumor biology, including during invasion. Using oral squamous cell carcinoma (OSCC) cells as a model, we examined whether and how CAFs respond to inflammatory signals to influence cancer cell migration and invasion. MATERIALS ANDMETHODS:
Chemokine signatures within the human HNSCC datasets from The Cancer Genome Atlas (TCGA) were analyzed together with tissue assessment using immunohistochemical staining (IHC) and real-time PCR. A co-culture system was used to identify reciprocal effects exerted by CAFs and cancer cells upon one another. Recombinant CXCL1, CXCL1 neutralizing antibodies, and CXCR2 antagonist were used to confirm CXCL1/CXCR2 axis-mediated cell behaviors.RESULTS:
Analysis of the TCGA dataset revealed that CXCL1 is associated with poor survival, and IHC demonstrated CXCL1 is highly expressed in OSCC stromal cells. Moreover, real-time PCR showed that in addition to CXCL1, IL-1ß and CXCR2 are also highly expressed in OSCC and IL-1ß mRNA levels positively correlate with CXCL1 expression. Furthermore, CAFs co-cultured with SAS, a poorly differentiated OSCC cell line, or stimulated with IL-1ß exhibit increased CXCL1 secretion in an NF-κB-dependent manner. Treatment of SAS cells with CAF-conditioned medium or CXCL1 increased their invasion and migration capabilities, indicating a reciprocal activation between CAFs and cancer cells. Moreover, CXCL-1 upregulated matrix metalloprotease-1 (MMP-1) expression and activity in CAFs.CONCLUSION:
The induction of IL-1ß following CXCL1 stimulation of CAFs mediates cancer cell invasion, and there is a reciprocal dependency between CAFs and cancer cells in the OSCC microenvironment.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Mouth Neoplasms
/
Carcinoma, Squamous Cell
/
Paracrine Communication
/
Chemokine CXCL1
/
Cancer-Associated Fibroblasts
Type of study:
Risk_factors_studies
Limits:
Humans
Language:
En
Journal:
Oral Oncol
Journal subject:
NEOPLASIAS
Year:
2019
Document type:
Article
Affiliation country:
Taiwan